This is an application for a grant to carry out research on methods for the synthesis of strigol. Strigol is a particularly potent germination stimulant for the parasite witchweed (Striga lutea Lour.), being able to cause 50% germination of witchweed seeds when applied in ca. 10-11M solution. It or analogous substances are present in a wide number of plant species. Its effects in other plant, animal, microbial, and viral systems have not been studied, since only trace amounts can be obtained from present plant sources. Pure strigol, C19H2206, was isolated at the Research Triangle Institute and its structure elucidated (see manuscript attached to this application). Its most significant structural feature is a substituted alpha-methylene-gamma-lactone combined with a gamma-lactol. The alpha-methylene-gamma-lactone moiety has been found essential for cytotoxic activity in a group of sesquiterpene lactones and was present in all of those active against in vivo tumor systems. The objective of the proposed research is to develop methods suitable for the synthesis of strigol and analogous compounds, so as to make them available for testing in various animal, microbial, and viral systems. It is proposed to carry this out by synthesis of the two principal moieties of the compound, which are then joined. Alternative routes to both moieties are considered, utilizing presently known compounds and synthetic methods where applicable, together with methods based upon analogy and mechanistic considerations. Stereochemical control of the synthetic steps and flexibility of the routes are given priority in the planning. Compounds and intermediates prepared will be submitted to testing for cytotoxicity, antimicrobial, antiviral, and anticancer activity, and seed germinating activity.